Project Summary: The Kansas City-New Vaccine Surveillance Network (KC-NVSN) program was established in 2009 to conduct population-based, laboratory-confirmed, active surveillance of acute gastroenteritis (AGE) illness in children seeking care at Children's Mercy Hospital, in Kansas City (KC), MO. The program was subsequently expanded in 2015 to include hospitalized ARI children in inpatient (IP) settings. In the current proposal, the KC-NVSN program seeks to continue the existing pediatric AGE IP and outpatient (OP) surveillance in the six county KC metropolitan area and ARI IP surveillance in Jackson County, MO. In addition, we will expand ARI surveillance to OP from Jackson County visiting the main CMH emergency department. Age and time matched healthy control children will also be enrolled. Eligible children visiting or admitted to our hospital system as defined above will be enrolled using permission and assent forms approved by the institutional review board (IRB) of CMH. We will conduct parent interviews, collect medical chart data and retrieve hard copies of vaccine information for influenza and rotavirus from enrolled children. Clinical specimens collected from children will be tested for rotavirus (and other GI pathogens, e.g. norovirus in proposed subprojects) in stool and 22 respiratory pathogens from respiratory specimen including specific influenza subtypes and other non-influenza viruses, such as RSV, EV-D68 etc. The data collected from the KC-NVSN program will provide population-based estimates to address the following specific aims: 1. To assess vaccine effectiveness (VE) in preventing medically attended rotavirus and influenza illness by the test-negative case-control study design using laboratory confirmed testing among enrolled children. 2. To assess the burden of select AGE pathogens and non-influenza viral pathogens, including respiratory syncytial virus and EV-D68 among enrolled children. The KC-NVSN program will provide data to be combined with other geographically diverse sites to estimate the national incidence, burden, and etiology of community-acquired AGE and ARI. The VE for rotavirus and seasonal influenza vaccinations will be calculated to measure the impact of vaccination. This network will also address several important scientific questions related to natural history of pediatric infectious diseases, transmission dynamics, impact of vaccine on targeted and vulnerable population and factors that influence vaccine effectiveness. The surveillance data generated from this network will provide timely and highly useful data to inform public health measures and pediatric vaccine-related policies aimed at controlling AGE and ARI in US children.